Not applicable.
Effective prophylactic or therapeutic treatment or diagnosis of many illnesses or conditions requires that a relatively constant level of therapeutic or diagnostic agents be administered in vivo. Before the development of time-release delivery systems, prophylactic, therapeutic and diagnostic agents were commonly administered as several doses at regular intervals. However, this mode of administration provides fluctuating levels of these agents.
Sustained release formulations have been prepared to provide a relatively constant release of prophylactic, therapeutic and diagnostic agents. Some of these formulations use biodegradable substances, such as poly(lactide) (PLA) or poly(lactide-co-glycolide) (PLGA) microspheres or films containing the agent to be administered. A relatively steady release of incorporated agents is possible using these microspheres and/or films by taking advantage of the near linear degradation profile of these polymers. However, in some cases, the in vivo release of incorporated agents from biodegradable polymers is initially high or low, and therefore non-uniform throughout the life of the delivery device. Furthermore, some polymers can substantially degrade after a period of hydration, which can substantially limit the effective life of the controlled release devices. Accordingly, several attempts have been made to modulate the controlled release of incorporated agents from biodegradable polymers to provide a higher level of initial medicament release and to provide longer periods of fairly consistent medicament release levels in vivo.
U.S. Pat. No. 4,919,939 to Baker describes polymeric sustained release drug delivery systems for placement in the periodontal pocket. Baker""s system incorporates drug-containing microparticles in a carrier medium and is effective for up to 30 days. However, a limitation of the device is that useful diffusion rates through the polymers are generally limited to drugs with molecular weights less than about 300.
U.S. Pat. No. 4,666,897 to Golub et al. teaches sustained release devices made from ethylene vinyl acetate (EVA) for sustained delivery of tetracycline. However, the EVA fibers are non-degradable and therefore must be physically removed after delivery of the therapeutic.
It is therefore an object of this invention to provide compositions for modulated release of an incorporated agent, wherein the composition includes a wide range of biocompatible polymers.
It is another object of this invention to provide biodegradable polymeric compositions for modulated release of an incorporated agent.
Sustained delivery compositions which modulate the release of incorporated prophylactic, therapeutic and/or diagnostic agents, and methods of preparation and use thereof, are disclosed. The compositions include a biocompatible polymeric matrix, a prophylactic, therapeutic, and/or diagnostic agent dispersed within the polymeric matrix, and a monovalent cation component which is separately dispersed within the polymeric matrix. The monovalent cation component modulates the release of the incorporated agent from the polymeric matrix.
The compositions can be prepared by dissolving a biocompatible polymer in a solvent to form a polymer solution, and separately dispersing a monovalent cation and a prophylactic, therapeutic, and/or diagnostic agent within the polymer solution. The polymer solution is then solidified to form a polymeric matrix. At least a significant amount of the monovalent cations is dispersed in the polymeric matrix separately from the incorporated agent. The cation modulates the release of the incorporated agent from the polymeric matrix.